Abstract
BackgroundMicroglia are highly motile phagocytic cells in the healthy brain with surveillance and clearance functions. Although microglia have been shown to engulf cellular debris following brain insult, less is known about their phagocytic function in the absence of injury. Propofol can inhibit microglial activity, including phagocytosis. Milk fat globule epidermal growth factor 8 (MFG-E8), as a regulator of microglia, plays an essential role in the phagocytic process. However, whether MFG-E8 affects the alteration of phagocytosis by propofol remains unknown.MethodsMicroglial BV2 cells were treated with propofol, with or without MFG-E8. Phagocytosis of latex beads was evaluated by flow cytometry and immunofluorescence. MFG-E8, p-AMPK, AMPK, p-Src, and Src levels were assessed by western blot analysis. Compound C (AMPK inhibitor) and dasatinib (Src inhibitor) were applied to determine the roles of AMPK and Src in microglial phagocytosis under propofol treatment.ResultsThe phagocytic ability of microglia was significantly decreased after propofol treatment for 4 h (P < 0.05). MFG-E8 production was inhibited by propofol in a concentration- and time-dependent manner (P < 0.05). Preadministration of MFG-E8 dose-dependently (from 10 to 100 ng/ml) reversed the suppression of phagocytosis by propofol (P < 0.05). Furthermore, the decline in p-AMPK and p-Src levels induced by propofol intervention was reversed by MFG-E8 activation (P < 0.05). Administration of compound C (AMPK inhibitor) and dasatinib (Src inhibitor) to microglia blocked the trend of enhanced phagocytosis induced by MFG-E8 (P < 0.05).ConclusionsThese findings reveal the intermediate role of MFG-E8 between propofol and microglial phagocytic activity. Moreover, MFG-E8 may reverse the suppression of phagocytosis induced by propofol through the regulation of the AMPK and Src signaling pathways.
Highlights
Microglia, resident macrophages of the central nervous system (CNS), account for 5–12% of brain cells [1] and mediate principal immune activities [2]
Microglia phagocytosis in response to propofol The viability of BV2 cells was measured after treatment with propofol (12.5 μM, 25 μM, 50 μM, and 100 μM) for 4 h (Fig. 1)
Our results showed that propofol did not significantly influence cell viability, compared with control (P > 0.05)
Summary
Resident macrophages of the central nervous system (CNS), account for 5–12% of brain cells [1] and mediate principal immune activities [2]. Previous studies have found that microglial clearance ability might be influenced by some medical agents, leading to subsequent neurological disorders [5, 6]. This evidence highlights the importance of the phagocytic function of resting microglia in maintaining CNS homeostasis and suggests that the mechanisms of phagocytosis may represent possible therapeutic targets. Whether MFG-E8 affects the alteration of phagocytosis by propofol remains unknown
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